At clinical sites around the world including Japan, diagnosis of heart failure is widely performed by measuring the blood levels of B-type natriuretic hormone (BNP) that is a hormone secreted mainly by cardiac myocyte. All over the world, it has been verified that there is a very strong correlation between the blood levels of BNP and the severity of chronic heart failure, and therefore BNP is the only biomarker currently used to assess the severity of heart failure.
A method for diagnosis of heart failure used at clinical sites has been almost established. More specifically, the blood levels of BNP are measured by an immunochemical method such as EIA or ELISA, and when the levels of BNP are 100 pg/mL or higher or 150 pg/mL or higher, a diagnosis of “suspected heart failure” is generally made. On the other hand, when the levels of BNP are equal to or less than 18.4 pg/mL that is the upper limit of the reference value of BNP, a diagnosis of “nothing abnormal detected” is generally made, and when the levels of BNP are in the range between thresholds (more specifically, 18.4 pg/mL to 100 pg/mL or 18.4 pg/mL to 150 pg/mL), there is a general clinical suspicion of some kind of cardiovascular disease, and therefore a diagnosis of “follow-up required and, if necessary, further examination” is made.
Among cardiovascular diseases, ischemic heart disease is clinically diagnosed by an outpatient examination such as electrocardiography, exercise electrocardiography, or echocardiography. However, it is difficult to completely detect ischemic heart disease by such an examination, and therefore it is usually necessary to perform a cardiac catheterization test requiring hospital admission for accurate diagnosis.
As nondrug treatment of ischemic heart disease, surgery to widen a stenotic area in the coronary artery is generally performed. An example of such surgery widely performed includes percutaneous coronary intervention (PCI). It is conventionally known that restenosis of a widened vessel occurs in about 20 to 40% of patients who underwent PCI within 3 to 6 months after PCI. However, in recent years, the frequency of restenosis has been reduced to as low as 10% or less by using a drug-eluting stent (DES) in this surgery.
On the other hand, U.S. Pat. No. 7,341,838 and JP-T-2006-527190 have recently disclosed a method for classifying a disease state of a test sample by specifically measuring the amount of at least one BNP polypeptide selected from the group consisting of BNP 79-108, BNP 77-106, BNP 39-86, BNP 53-85, BNP 66-98, BNP 30-106, BNP 11-107, BNP 9-106, BNP 69-100, BNP 76-107, BNP 69-108, BNP 80-108, BNP 81-108, BNP 83-108, BNP 30-103, BNP 3-108, and BNP 79-106 (herein, a BNP precursor composed of 108 amino acids is expressed as BNP 1-108, based on which these BNP polypeptides are expressed) contained in the test sample. More specifically, these documents describe that BNP 3-108 may distinguish unstable angina or myocardial infarction from congestive heart failure, which is based on the result of analysis of test samples derived from a patient having a BNP value of 353.5 pg/mL and from a patient having a BNP value of 905.5 pg/mL.
Further, JP-A-2007-322187 has recently disclosed a method for measuring the blood levels of modified low-density lipoprotein (modified LDL) as an example of a method for assessing the risk of development of restenosis after PCI.    Patent Document 1: U.S. Pat. No. 7,341,838    Patent Document 2: JP-T-2006-527190    Patent Document 3: JP-A-2007-322187